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To compare the performance of patient- and physician-obtained cytology and human papillomavirus (HPV) testing for the detection of high-grade cervical intraepithelial neoplasia.A cross-sectional study was performed involving 334 women seen at three colposcopy clinics (Tucson, Arizona; Hermosillo, Mexico; and Lima, Peru). All women used a cytobrush to self-collect specimens for cervical cytology and HPV testing. Subjects subsequently underwent physician collection for cytology and HPV, followed by a complete colposcopic evaluation with directed biopsy. Cytology was processed using thin-layer technology, and HPV was determined using the polymerase chain reaction technique. Test performance characteristics were determined using the histopathologic diagnosis as the reference standard and designating high-grade cervical intraepithelial neoplasia as clinically significant disease for the purpose of the analysis.The sensitivity of patient-collected cytology was significantly lower (55.0%) and specificity was significantly better (84.1%) than those of physician-directed sampling (85.2% and 73.4%, respectively). Patient-collected HPV had significantly lower sensitivity (49.0%) than physician sampling (82.2%), although specificity did not significantly differ.Patient collection is a feasible although inferior alternative to physician-collected cervical cytology and HPV testing.